Are statins (HMG-CoA reductase inhibitors) safe for patients with liver issues, such as hepatic impairment?

From the Guidelines

Statins can be used safely in patients with liver issues, including those with mild to moderate liver disease, under close monitoring and with careful consideration of the potential risks and benefits. For those with mild to moderate liver disease, low-dose statins like atorvastatin 10-20 mg daily or rosuvastatin 5-10 mg daily can often be used safely with regular monitoring 1. Pravastatin and pitavastatin may be preferred options as they undergo less hepatic metabolism. Before starting therapy, baseline liver function tests should be obtained, with follow-up testing at 4-12 weeks and then periodically (every 3-6 months) during the first year. If liver enzymes rise to more than 3 times the upper limit of normal, the statin should be temporarily discontinued or the dose reduced. The benefits of statins for cardiovascular risk reduction often outweigh the risks, even in patients with stable liver disease, as stated in the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1.

Some key points to consider when using statins in patients with liver issues include:

• Statins are not contraindicated in patients with increased ASCVD risk with chronic, stable liver disease, and limited data suggest potential benefit 1.
• Severe statin-associated hepatotoxicity is rare, and the incidence is not impacted by routine monitoring of transaminases 1.
• An asymptomatic increase in transaminases (>3 times upper limit of normal) is an infrequent statin-associated side effect that often resolves with dose reduction or rechallenge with alternative statins 1.
• Regular monitoring and coordination between primary care providers and specialists are essential for managing these patients effectively.

However, statins should be avoided in patients with acute liver failure, decompensated cirrhosis, or active alcoholic liver disease. In patients at increased ASCVD risk with severe statin-associated muscle symptoms or recurrent statin-associated muscle symptoms despite appropriate statin rechallenge, it is reasonable to use RCT proven nonstatin therapy that is likely to provide net clinical benefit 1.

From the FDA Drug Label

Pitavastatin tablets is contraindicated in patients with acute liver failure or decompensated cirrhosis [see Contraindications (4)] . Consider liver enzyme testing before the initiation of pitavastatin tablets and when clinically indicated thereafter Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury.

Statin use in patients with liver issues is approached with caution.

• Contraindications: Pitavastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis.
• Precautions: Patients with a history of liver disease or substantial alcohol consumption may be at increased risk for hepatic injury.
• Monitoring: Liver enzyme testing should be considered before initiating pitavastatin and when clinically indicated thereafter. Pitavastatin may be used in patients with liver issues, but with careful monitoring and consideration of the potential risks 2.

From the Research

Statin Use in Patients with Liver Issues

• Statins can be used in patients with liver disease, but caution is needed and liver toxicity should always be monitored during statin treatment 3.
• The benefits of statins likely outweigh the risks in the large majority of dyslipidemic patients affected by non-alcoholic hepatosteatosis, a disease frequently diagnosed in insulin-resistant subjects 3.
• Statins are generally well tolerated in patients with chronic liver disease such as nonalcoholic fatty liver disease (NAFLD), primary biliary cirrhosis, and hepatitis C virus 4.
• Decompensated cirrhosis and acute liver failure should be considered contraindications for lipid-lowering therapy as these patients are unlikely to benefit because of their generally grave prognosis 4.

Safety of Statin Therapy

• Results from studies of statin therapy in patients with elevated liver enzyme levels, nonalcoholic fatty liver disease, hepatitis C, cirrhosis, liver transplants, and hepatocellular carcinoma show benefit without increased risk of adverse effects 5.
• Statin therapy should not be withheld in patients with liver disease, however, more robust, prospective clinical trials are needed to confirm the safety and efficacy 5.
• There is robust evidence that supports the safety of statins in patients with liver disease in the absence of severe liver dysfunction 6.

Specific Considerations

• Compensated cirrhosis is not a contraindication for statin use, but decompensated cirrhosis requires extreme caution and frequent monitoring of creatinine phosphokinase levels 6.
• Statins may be beneficial in patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), and may reduce cardiovascular disease events and protect from hepatocellular carcinoma (HCC) related to NAFLD/NASH 7.
• Specific statins such as atorvastatin and rosuvastatin may offer substantial liver- and CVD-related adverse event reduction in patients with NAFLD/NASH 7.